Doxorubicin and paclitaxel enhance the antitumor efficacy of vaccines directed against HER 2/neu in a murine mammary carcinoma model

INTRODUCTION: The purpose of the present study was to determine whether cytotoxic chemotherapeutic agents administered prior to immunotherapy with gene vaccines could augment the efficacy of the vaccines. METHODS: Mice were injected in the mammary fat pad with an aggressive breast tumor cell line that expresses HER2/neu. The mice were treated 3 days later with a noncurative dose of either doxorubicin or paclitaxel, and the following day with a gene vaccine to HER2/neu. Two more doses of vaccine were given 14 days apart. Two types of gene vaccines were tested: a plasmid vaccine encoding a self-replicating RNA (replicon) of Sindbis virus (SINCP), in which the viral structural proteins were replaced by the gene for neu; and a viral replicon particle derived from an attenuated strain of Venezuelan equine encephalitis virus, containing a replicon RNA in which the Venezuelan equine encephalitis virus structural proteins were replaced by the gene for neu. RESULTS: Neither vaccination alone nor chemotherapy alone significantly reduced the growth of the mammary carcinoma. In contrast, chemotherapy followed by vaccination reduced tumor growth by a small, but significant amount. Antigen-specific CD8(+ )T lymphocytes were induced by the combined treatment, indicating that the control of tumor growth was most probably due to an immunological mechanism. The results demonstrated that doxorubicin and paclitaxel, commonly used chemotherapeutic agents for the treatment of breast cancer, when used at immunomodulating doses augmented the antitumor efficacy of gene vaccines directed against HER2/neu. CONCLUSIONS: The combination of chemotherapeutic agents plus vaccine immunotherapy may induce a tumor-specific immune response that could be beneficial for the adjuvant treatment of patients with minimal residual disease. The regimen warrants further evaluation in a clinical setting

Adaptive responses among Dutch elderly: the impact of eight chronic medical conditions on health-related quality of life.

OBJECTIVES: This study analyzed the impact of eight common chronic medical conditions on functional, social, and affective domains of health-related quality of life among community-based Dutch elderly (n = 5279). METHODS: Health-related quality of life was measured with six domains of the MOS Short-Form General Health Survey. The impact of the selected chronic conditions on health-related quality of life was analyzed by means of Student's t tests, analyses of variance, and multiple regression analyses. RESULTS: Compared with other domains of health-related quality of life, mental health was the least affected by chronic medical conditions. Back problems and rheumatoid arthritis/other joint complaints accounted for relatively high proportions of the variance in health-related quality of life (from 35.5% to 68.3%), except for health perceptions (22.6%), indicating that health-related quality of life is most affected by these two conditions. CONCLUSIONS: Subjective well-being is by far the domain least affected by chronic medical conditions, while physical functioning and health perceptions are most affected. Back problems and rheumatoid arthritis/other joint complaints affect health-related quality of life strongly

Functioning, well-being, and health perception in late middle- aged and older people: comparing the effects of depressive symptoms and chronic medical conditions

OBJECTIVES: To expand the landmark Medical Outcomes Study (MOS) and World Health Organization (WHO) findings on the unique association of symptoms of depression with multiple domains of functioning, health perception, and well-being in consulting populations to the late middle- aged and older community-dwelling population and to contrast this unique association to that of specific chronic medical conditions and sensory and cognitive impairment (collectively denoted as medical conditions (MCs)). DESIGN: Population-based, cross-sectional health survey. SETTING AND PARTICIPANTS: A total of 5279 noninstitutionalized late middle-aged and older persons living independently or in residential homes for older people housing in the northern part of The Netherlands. MEASUREMENTS: Behavioral: physical functioning, (Independent) Activities of Daily Living ((I)ADL), and role functioning. Subjective: health perception, life satisfaction and well-being. Mixed: discretionary activities and activity level. Two aspects of the association were examined: the unique risk (adjusted difference in mean outcome between those with the condition and those without, expressed in SD units) and the unique contribution (adjusted proportion of variance in outcome accounted for by the condition). The latter takes the prevalence of the condition into account. RESULTS: Among both individuals with MCs and those without, persons with symptoms of depression did worse on all outcomes than those without. Depressive symptoms were more consequential for subjective and mixed outcomes compared with behavioral outcomes. For all outcomes, none of the unique contributions of MCs exceeded that of depressive symptoms, whereas the unique contribution of depressive symptoms typically outranked those of the MCs. For behavioral outcomes, the unique risks associated with neurological conditions, persistent back problem, arthritis, and stroke exceeded that of depressive symptoms, but risk associated with depressive symptoms exceeded that of nine of 18 MCs, on average. For the mixed and subjective outcomes, none of the unique risks associated with MCs exceeded that of depressive symptoms, but risks of depressive symptoms exceeded those of 16 of the 18 MCs, on average. The effects of depressive symptoms and medical conditions were largely additive although depressive symptoms amplified the effect of some medical conditions on (I)ADL. The pattern of unique risks and contributions was similar across all ages (57-64, 65-74, 75+). CONCLUSION: The unique contribution of depressive symptoms in dysfunction, poor health perception, and well-being typically exceeds that of medical conditions because depressive symptoms combine a moderately large unique risk with a rather high prevalence. Results expand the MOS and WHO findings to the community- dwelling late middle-aged and older population and to additional outcomes as well. Results underscore the importance of detection and management of (comorbid) symptoms of depression in older people

Functional optical coherence tomography of pigmented lesions

Background: Cutaneous melanomas are diagnosed worldwide in 231,130 patients per year. The sensitivity and specificity of melanoma diagnosis expresses the need for an additional diagnostic method. Optical coherence tomography (OCT) has shown that it allows morphological (qualitative) description of image features and quantitative analysis of pathology related light scattering by means of the attenuation coefficient (μoct ). Objective: We hypothesize that OCT images of nevi will differ qualitatively and quantitatively from melanomas. Methods: Forty lesions from 33 consecutive patients were imaged with OCT. After data acquisition, excision was performed. Epidermal layer thickness was measured and values of μoct were extracted from 200 OCT images of pigmented lesions. Results: Morphologically, absence of the lower border of the lesion was characteristic for melanoma (P = 0.02). Also, the μoct was different between benign and malignant lesions (P = 0.02). There were no differences in epidermal layer thickness of benign lesions and melanoma. Conclusion: Although this preliminary study comprised a small number of patients, quantitative analysis of OCT images in pigmented skin lesions give valuable additional information about lesions characteristics. When using the attenuation coefficient, it might be possible to distinguish between benign lesions and melanomas.R. Wessels, D.M. de Bruin, G.N. Relyveld, D.J. Faber, A.D. Vincent, J. Sanders, T.G. van Leeuwen, T.J.M. Ruer